Synthesis, Theory and In Vitro Photodynamic Activities of New Copper(II)-Histidinito Complexes

摘要

The photo-dynamic effect of four new copper(II)-histidinito complexes with phenanthroline-based ligands were studied in details. All the complexes were tested against HeLa (Human Cervical Carcinoma) and 3T3 (normal fibroblast) cells both in dark and in visible light. Although the complexes were toxic to HeLa cells (IC50 ~ 10 μM), visible light (400-700 nm) remarkably enhanced the cytotoxicity of the complexes to the extent of sub-micromolar level. Several photo-physical measurements along with the Time-dependent density functional theory (TDDFT) calculations rationalize the level of photodynamic therapy (PDT) effect of the complexes, which is related to the generation of singlet oxygen (1O2) on photo-activation. Presence of low lying, long-lived triplet excited states facilitating the effective intersystem crossing was responsible for generation of higher level of singlet oxygen in pyrenyl complex. High level of reactive oxygen species (ROS) on photo-activation is primarily responsible for apoptotic photo-cytotoxicity. Fluorescence microscopy revealed the cytosolic localization of the complex.Overall results are of paramount importance towards designing of next generation metal-based PDT agents as the viable alternatives of porphyrins.